A Method to Analyze Models of the Dynamics of Germinal Centers.

Germinal centers (GC) are dynamic, short-lived anatomical structures generated within lymphoid follicles during immune responses to protein-containing antigens. There, follicular dendritic cells, antigen-specific B cells, and follicular T helper cells engage with each other in an antigen dependent way, setting into play a mini-evolutionary ecosystem that ultimately lead to antibody affinity maturation, with the resulting GC reaction following a rise-and-fall dynamics. The complexity of the cell-to-cell interaction processes makes very difficult to mechanistically understand the GC dynamics. Different mathematical or computational models have been or can be developed to help clarify the mechanisms driving and regulating the GC dynamics. However, the very important question of which are the dominant model parameters is not frequently studied for most of those models. Here we describe in detail one method to perform such a parameter analysis-known as parameter sensitivity analysis-which can be applied to many models of the GC dynamics.